Studies were conducted to determine the effects of parenteral therapy with indomethacin, ibuprofen, and piroxicam on key immunologic and hematologic alterations induced by thermal injury in a guinea pig model and on survival following experimental burn wound infection with Pseudomonas aeruginosa and Proteus mirabilis. Drugs (10-20 mg/kg) or placebo were administered intramuscularly to thermally injured guinea pigs at 3 hr postburn and then daily for nine days postburn. All three drugs inhibited production of prostaglandin F alpha and thromboxane B2 in wound fluid and concomitantly restored the bactericidal activity of polymorphonuclear leukocytes (PMNs) against P. aeruginosa to normal. Indomethacin increased the proliferative response of splenic lymphocytes to concanavalin A at a dose of 10 mg/kg but not 20 mg/kg, and ibuprofen and piroxicam had no effect on this response. None of the drugs affected the extent of systemic complement consumption, thrombocytopenia, leukocytosis, or leukopenia in the injured animals, or survival following burn wound infection with P. aeruginosa or P. mirabilis. These results suggest that the PMN bactericidal defect induced by thermal injury is preventable or reversible, and that the mechanisms responsible for this defect are inhibitable by nonsteroidal anti-inflammatory drugs. Keywords: Immunity, Immunosuppression.